Patent SG-11201903676S-A (SG)
Title: Genetically modified mouse model for human hepatocyte xenotransplantation
Inventor: SHULTZ LEONARD
IPC: C12N15/113
Filed: 2017-10-27
Abstract: xi6 hepatocytes NSG-PiZ F1-88-GFP FIG. la (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 03 May 2018 (03.05.2018) WIPO I PCT 0111111010 0111 °nolo III m VIII 0111 oimIE (10) International Publication Number WO 2018/081561 Al (51) International Patent Classification: C07K 14/81 (2006.01) C12N 15/113 (2010.01) C12N 5/071 (2010.01) C12N 15/86 (2006.01) (21) International Application Number: PCT/US2017/058758 (22) International Filing Date: 27 October 2017 (27.10.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/413,736 27 October 2016 (27.10.2016) US 62/413,743 27 October 2016 (27.10.2016) US (71) Applicant: THE JACKSON LABORATORY [US/US]; Published: 610 Main Street, Bar Harbor, ME 04609 (US). (72) Inventor: SHULTZ, Leonard, D.; 80 Indian Point Rd., Bar Harbor, ME 04609 (US). (74) Agent: STAPLE, Julie, K. et al.; Dinsmore & Shohl LLP, 900 Wilshire Drive, Suite 300, Troy, MI 48084 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — of inventorship (Rule 4.17(iv)) with international search report (Art. 21(3)) with sequence listing part of description (Rule 5.2(a)) = (54) Title: GENETICALLY MODIFIED MOUSE MODEL FOR HUMAN HEPATOCYTE XENOTRANSPLANTATION 00 O 00 O C (57) : One or more embodiments of the present invention include an immunodeficient mouse genetically modified to include a gene encoding a PiZ variant (G1u342Lys) of human ct-1 antitrypsin (AAT), wherein the mouse expresses the PiZ variant of human ct-1 antitrypsin (Z-AAT), and has a reduced number of mouse hepatocytes compared to an immunodeficient mouse of the same type which does not express Z-AAT. The immunodeficient mouse genetically modified to include a gene encoding a PiZ variant of human AAT can be a genetically modified NSG, NRG or NOG mouse. The immunodeficient mouse may further include xenogeneic hepatocytes, such as human hepatocytes. Putative treatments of human liver disease can be assessed in mice provided according to aspects of the present disclosure.